Methods of preparing sulphanilylalkylisoureas



Patented Aug. 29, 1944 UNITED? STATES PATENT OFF-ICE.

METHODS OF PREPARING SULPHANILYLALP KYLISOUREAS Richard Owen Roblin, Jr., Old Greenwich, and George Washing-ton Anderson, Stamford, Conn, assignors' to American Cyanamid Company, New York, N; Y., a corporation of Maine.

No Drawing. Application January 31 1942,

Serial No. 429,134

- Claims; (01. zoo -3am).

This invention relates to a new andimproved process for producing p-aminobenzenesulphonylalkylisoureas.

The compounds which canbe preparedby the; process of the present invention have the following general, formula:

in which R is amino or nitro and R"isan alkyl' spending acylsulphanilyl' chloride with calciumcyanainide. 1 a

The invention will be described in greater detail in conjunction with the following specific examples which illustrate the production of typical isoureasl, Thepartsare. by weight.

use the sodium or calcium salts as these are the cheapest; talnable with the corresponding potassium salts.

In the modification. of the present invention starting with the acylsulphanilyl cyanamide salt the acyl group is' not particularly important.

Anyof the ordinary acyl groups such. as acetyl, propio-nyl, benzoyl and the like may be used. Since however; the acetyl group is not hydrolyzed and therefore does not affect the chemical structure of the final product; it is preferabl'e to utilize the cheapest and most' readilyavailable acyl group, namely the acetyl group.

The nitrobenzenesulphonylisoureas may then be transformed into the corresponding p-amino compounds by reduction. The technique of reduction is similar to that employed in the production of other aminobenzenesulphonamide compounds and it is an advantage that the present invention requires no new technique in this step.

The 'alkyl group of the isourea depends of course, on the alcohol used in the reaction and in general any of the common reacted alcohols may be used such as lower paraflln or other aliphatic alcohols, benzyl alcohol and the like.

The present invention is not concerned with any particular method of preparing the raw materials entering into the reaction and the sodium nitrobenzene cyanamide may for example, be prepared as described in our Patent No. 2,259,721 of October 21, 1941. The acylsulphanilylcyanamide may be prepared by reacting the corre- However, the same results are oh-l Example 1 p-Nltrobenzenesulphonylmethylisourea 14.9\ parts of sodium p-nitrobenzenesulphonylcyanamidevwere added to. 100 parts of meth.-- anolv and: 8?. partsof hydrogen, chloride were bubbled in; a white precipitate formed. After standing at roomtemperature in a. stoppered flask for one and one-half hours; the solid was filtered o-ff, slurried with water made slightly alkaline with ammonium hydroxide, re-filtered and washed. Recrystallization from. methanol gave colorless crystals having a melting point of about 203-6 0.

Example 2 Sulphanilylmethylisourea 5.3 parts of" p-nitrobenzenesulphonylmethyl isourea were. added. to. awarmed mixture of 14.5.1 parts of ironpowder and 28.,parts of'5% acetic acid. The, mixture. was. heated on a steam bath, for one-half hour, cooled and extracted with two portions of 10% sodium hydroxide, each of 0 parts. Neutralization of the extracts with hydrochloric acid (the product was soluble in an excess of acid) gave a precipitate. Recrystallization from water and from isopropyl alcohol,

Example 3 Sulphanilylmethylisourea NH SOzNH.C-OOH:

Sulphanilylmethylisourea may also be obtained ,by passing 8 parts of hydrogenchloride into a ide.

mixture of 100 parts of methanol and 26 parts of calcium acetylsulphanilylcyanamide (omooNHC so2N .oN

The resulting mixturewas allowedto stand 4 hours, then filtered after dilution with an equal volume of water. Upon making slightly alkaline with ammonium hydroxide, a precipitate of sulphanilylmethylisourea formed. I

Example 4 p-NitrobenZenesulphonylethylisourea Sulphanilylethylisourea NH OSOzNHO- -O 0112011;

12.5 parts of p+nitrobenzenesulphonylethylisourea were added to a warrnmixture of 38.5 parts of iron dust and 88 parts of 5% acetic acid. After off; more was obtained by partial evaporation of the filtrate under vacuum. Recrystallization from dilute alcohol resulted in colorless crystals of melting point about 113-114: C.

Example 7 Sulphanilylisopropylisourea NH NHZQSOZNHA i-QOMCHQ 1.7 parts of the nitro compound from Example 6 were added to 3.3 parts of iron dust and 7.2 parts of 5% acetic acid. The mixture was evaporated to dryness on the steam bath and the residues were extracted with 10% sodium hydroxide. On neutralization with hydrochloric acid, a precipitate of sulphanilylisopropylisourea was obtained. Purification by recrystallization from dilute methanol, using decolorizing carbon, and

from benzene yielded colorless crystals having a.

melting point of about 104-5 C.

We claim:

1. A method of producing a sulph'anilylis'ourea having the following formula;

in which R is a hydrocarbon radical which com- ;gpgprises reacting a salt of an acylsulphanilylcyanheating on the steam bath for half an hour, the

mixture was extracted with 10% sodium hydrox- Neutralization of the extracts with hydrochloric acid yielded a precipitate of sulphanilylethylisourea which was purified by recrystallization from dilute alcohol or from benzene-'isopropyl acohol. Its melting point was about 127-8 C. r

- Example 6 p-nitrobenzenesulphonylisopropylisourea H rvmQsomnooonrom):

ide. Chilling gave a'precipitate which is filtered 12.5 parts of sodium p-nitrobenzenesulphonylcyanarnide were added to 20. parts of isopropyl alcohol plus 40 parts of dioxane. 5.5 parts of hydrogen chloride were passed in rapidly without cooling; the temperature rose to about 58 C. The mixture was allowed to stand at room,

temperature overnight. After filtering fromsome solid and solution with water, the solution was made slightly alkaline with ammonium hydroxamide with an alcohol in the presence of a hydrog'en halide.

2. A method of producing sulphanilylisourea having the following formula:

O in which R" is an alkyl group, which comprises reacting a salt of an acylsulphanilylcyanamide. with a parafifin alcohol in the presence of a hydrogen halide.

3. A method of preparing sulphanilylmethylisourea which comprises reacting a salt of an acylsulphanilylcyanamidewith methanol in the presence of hydrogen chloride. I

4. A method preparing sulphanilylethylisourea which comprises reacting a salt of an acy1sulph-,

anilylcyanamide with ethanol in the presence of. hyrogen chloride. I f I 5. A method of preparing sulphanilylisopropyliisourea which comprises reacting a salt of an acylsulphanilylcyanamide with isopropanol in the a presence of hydrogen chloride.

- RICHARD OWEN ROBLIN,JR, Q

GEORGE WASHINGTON ANDERSON CERTIFICATE OF CORRECTION.

August 29, 191414.

RICHARD OWEN ROBLIN, JR. ET AL.

Patent No. 2,556,9h9.

It is hereby certified that error appears in the printed specification of the above numbered. patent requiring correction as follows Page 2, first column, line L B, strike out "ide. Chilling gave a precipitate which is filtered" and insert the same after "hydrox" in line 57; and that the said Letters Patent should be read with this correction therein that the same may conform to the record of the case in the Patent Office.

Signed and sealed this lhth day of November, A. D. 19th.

Leslie Frazer a Acting Commissioner of Patents. 

